Literature DB >> 16103770

The normalized inhibitory quotient of boosted protease inhibitors is predictive of viral load response in treatment-experienced HIV-1-infected individuals.

Alan Winston1, Gill Hales, Janaki Amin, Erno van Schaick, David A Cooper, Sean Emery.   

Abstract

OBJECTIVE: The normalized inhibitory quotient (NIQ) has been proposed as a measure for refining the precision of HIV resistance testing when selecting antiretroviral therapy (ART). We undertook an assessment of NIQ and 48-week virological outcome in patients commencing ritonavir-boosted protease inhibitor (PI) regimens.
DESIGN: A cohort of 87 HIV-infected individuals who all had extensive prior exposure to ART were assigned a new boosted PI regimen following resistance testing. PI therapy consisted of lopinavir, indinavir, saquinavir and amprenavir at 50, 32, 11 and 6%, respectively. Fold change (FC) for each PI was determined from the resistance test at baseline. Trough drug concentration (Cmin) was determined at week 4.
METHODS: NIQ was derived individually by taking the logarithm of the ratio of Cmin/FC divided by the fixed ratio of population mean trough drug concentration/clinical cut off. Associations between viral load (VL) response over 48 weeks with baseline VL, FC, Cmin, NIQ and selected PI were assessed.
RESULTS: Mean change from baseline VL reduced by 0.83 log at week 48. In multivariate analyses, baseline VL and NIQ were the parameters most associated with change from baseline VL at week 48 (P = 0.012 and 0.003, respectively). FC, Cmin and selected PI were not significantly associated with VL changes.
CONCLUSION: In this cohort of highly treatment-experienced individuals treated with boosted PI regimens, baseline VL and NIQ were significantly predictive of virological response over 48 weeks whereas FC and Cmin were not. These results support the use of a NIQ at week 4, as a tool for predicting response to therapy in this setting.

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Year:  2005        PMID: 16103770     DOI: 10.1097/01.aids.0000181009.77632.36

Source DB:  PubMed          Journal:  AIDS        ISSN: 0269-9370            Impact factor:   4.177


  8 in total

1.  The design and implementation of A5146, a prospective trial assessing the utility of therapeutic drug monitoring using an inhibitory quotient in antiretroviral-experienced HIV-infected patients.

Authors:  Lisa M Demeter; A Lisa Mukherjee; Robin DiFrancesco; Hongyu Jiang; Robert DiCenzo; Barbara Bastow; Alex R Rinehart; Gene D Morse; Mary Albrecht
Journal:  HIV Clin Trials       Date:  2008 Jan-Feb

2.  Quality assessment for therapeutic drug monitoring in AIDS Clinical Trials Group (ACTG 5146): a multicenter clinical trial.

Authors:  Robin DiFrancesco; Susan Rosenkranz; A Lisa Mukherjee; Lisa M Demeter; Hongyu Jiang; Robert DiCenzo; Carrie Dykes; Alex Rinehart; Mary Albrecht; Gene D Morse
Journal:  Ther Drug Monit       Date:  2010-08       Impact factor: 3.681

3.  A randomized clinical trial evaluating therapeutic drug monitoring (TDM) for protease inhibitor-based regimens in antiretroviral-experienced HIV-infected individuals: week 48 results of the A5146 study.

Authors:  Mary Albrecht; A Lisa Mukherjee; Camlin Tierney; Gene D Morse; Carrie Dykes; Karin L Klingman; Lisa M Demeter
Journal:  HIV Clin Trials       Date:  2011 Jul-Aug

4.  Use of different inhibitory quotients to predict early virological response to tipranavir in antiretroviral-experienced human immunodeficiency virus-infected patients.

Authors:  Judit Morello; Carmen De Mendoza; Vincent Soriano; Lourdes Anta; Gema González-Pardo; Angélica Corral; Francisco Blanco; Inmaculada Jiménez-Nácher; Juan González-Lahoz; Sonia Rodríguez-Novoa
Journal:  Antimicrob Agents Chemother       Date:  2009-07-13       Impact factor: 5.191

5.  Novel method to assess antiretroviral target trough concentrations using in vitro susceptibility data.

Authors:  Edward P Acosta; Kay L Limoli; Lan Trinh; Neil T Parkin; Jennifer R King; Jodi M Weidler; Ighovwerha Ofotokun; Christos J Petropoulos
Journal:  Antimicrob Agents Chemother       Date:  2012-09-10       Impact factor: 5.191

6.  A randomized trial of therapeutic drug monitoring of protease inhibitors in antiretroviral-experienced, HIV-1-infected patients.

Authors:  Lisa M Demeter; Hongyu Jiang; A Lisa Mukherjee; Gene D Morse; Robin DiFrancesco; Robert DiCenzo; Carrie Dykes; Prakash Sista; Lee Bacheler; Karin Klingman; Alex Rinehart; Mary Albrecht
Journal:  AIDS       Date:  2009-01-28       Impact factor: 4.177

7.  A randomised trial comparing genotypic and virtual phenotypic interpretation of HIV drug resistance: the CREST study.

Authors:  Gillian Hales; Chris Birch; Suzanne Crowe; Cassy Workman; Jennifer F Hoy; Matthew G Law; Anthony D Kelleher; Douglas Lincoln; Sean Emery
Journal:  PLoS Clin Trials       Date:  2006-07-28

8.  Role of atazanavir in the treatment of HIV infection.

Authors:  Pablo Rivas; Judit Morello; Carolina Garrido; Sonia Rodríguez-Nóvoa; Vincent Soriano
Journal:  Ther Clin Risk Manag       Date:  2009-03-26       Impact factor: 2.423

  8 in total

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